1. Field
The present disclosure relates to 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone (Clomazone), an agricultural herbicide. The present disclosure relates in particular to novel crystalline polymorphs of clomazone, to processes for their preparation, and compositions comprising the same.
2. Description of Related Art
2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, a compound having the common name clomazone, is disclosed in U.S. Pat. No. 4,405,357. Its herbicidal properties are described. This herbicidal isoxazolidinone is represented by the following structural formula (I):

U.S. Pat. No. 4,405,357 discloses the preparation of clomazone. In particular, the following procedure to synthesize clomazone is disclosed:

A further process scheme is disclosed in U.S. Pat. No. 4,405,357, as follows:

However, the process yields the desired product in only a relatively low yield due to the formation of by products having the general formulae (II) and (III) as follows:

It is disclosed in U.S. Pat. No. 4,742,176 that the typical product mixture of the above process scheme includes the compounds of formulae (I), (II) and (III) in the ratio of (I):(II):(III) of about 85/10/5. It would be advantageous if an improved process could be found that yielded higher amounts of clomazone, with reduced formation of the by-products of formulae (II) and (III).
In addition, the process of U.S. Pat. No. 4,405,357 suffers an number of drawbacks. As indicated above, the reaction process utilizes methanol (MeOH) and dimethylformamide (DMF) as solvents. However, the use of the aforementioned solvents gives rise to a number of problems, in particular on a commercial scale of production. For example, methanol is a flammable, unsafe solvent with a low flash point and is a source for peroxide formation. As a result, the use of methanol in large-scale production is very limited. In addition, aprotic polar solvents, such as dimethyl formamide (DMF) are water-miscible and are typically recycled as azeotropes containing high amounts of water.
U.S. Pat. No. 4,742,176 discloses an improvement to the second process scheme of U.S. Pat. No. 4,405,357. In particular, the process is modified by contacting the product mixture with hydrogen chloride gas prior to isolating the desired product. This treatment converts the compound of formula (II) into a mixture of 4,4-dimethyl-3-isoxazolidinone and 2-chlorobenzyl chloride, which may be recycled with base to the desired product. The compound of formula (III) in the product is converted by contact with hydrogen chloride into other components, which are readily separated. Clomazone is not affected by contact with hydrogen chloride. As will be appreciated, these modifications result in a greater processing complexity and involve the use of additional components, in particular hydrogen chloride gas, which is undesirable.
To date, there are no simple methods for the synthesis of clomazone, which can be used on a large scale to produce the desired product to a high degree of purity.
There is thus an urgent and unmet need in the art for efficient methods for the preparation and purification of clomazone , which overcome the drawbacks and deficiencies of the prior art methods.
In addition, there are also no known crystalline polymorphic forms of clomozone.